3-甲基-8-喹啉磺酰氯的合成

Synthesis of 3-Methyl-8-quinolinesulphonyl Chloride

以硝基苯作为起始原料,经还原后,与2-甲基丙烯醛环合,再与氯磺酸反应制备得到阿加曲班的关键中间体3-甲基-8-喹啉磺酰氯,结构经1H NMR、ESI-MS等确证,并对合成工艺进行了优化。优化条件下,总收率达78.4%(以硝基苯计),纯度达98.6%(HPLC)。制备方法操作简单,反应条件比较温和,使用的起始物料和试剂廉价易得,可用于工业化生产。

3-Methyl-8-quinolinesulphonyl chloride,the key intermediate of Argatroban monohydrate was prepared from nitrobenzene via reduction,cyclisation with 2-methacroleim and sulfonyl chloride reaction.The structure of target compound was identified by'H NMR and ESI-MS The reaction conditions for the synthesis of 3-methyl-8-quinolinesulphonyl chloride were optimized.The total yield of this target compound was improved to 78.4%with a purity of 98.6%.The improved process is facile with relatively convenient operation procedures and suitable for industrial production.